DECREASE IN THE AIRWAYS NONADRENERGIC NONCHOLINERGIC INHIBITORY SYSTEM IN ALLERGEN SENSITIZED RABBITS

A decrease in the airways' nonadrenergic noncholinergic inhibitory (NA NC-i) system is one of the mechanisms that may contribute to allergen- induced changes in neural control within airways. We measured the airw ays' neurally mediated contractile and relaxant (NANC-i) responses in tracheal segments and left mainstem bronchus (LMB) from normal (contro l), immune (ragweed sensitized), and immune challenged rabbits. Immune rabbits were sensitized to mixed ragweed extract through parenteral i njections from birth, while the immune challenged group had an additio nal airway exposure to aerosolized ragweed 48 hours prior to the in vi tro studies; Neurally mediated contractile responses to electrical fie ld stimulation (EFS) were increased in the immune challenged group, wi th the increase most significant in tracheal smooth muscle at a stimul ation frequency of 20 Hz. To assess NANC-i responses, airway smooth mu scle (ASM) segments from these groups were placed in tissue baths cont aining atropine (10(-6) M) and propranolol (5 x 10(-6) M). After contr action of the tissue with neurokinin A (NKA, 10(-5) M), the NANC-i res ponse to EFS at 20 Hz was measured and reported as the mean (+/- SEM) percent relaxation. No significant differences were seen in the contra ctile responses of ASM segments to NKA among the three groups. The tra cheal segments showed a significantly different NANC-i relaxation resp onse among all groups: in the control group, 29.1 +/- 3.7; in the immu ne group 15.8 +/- 2.3%; and in the immune challenged group, 2.1 +/- 4. 2%. The LMB segments showed significantly different NANC-i responses b etween the immune challenged group (-3.4 +/- 2.5%) and both the contro l (13.4 +/- 5.7%) and immune group (9.5 +/- 2.9%). This NANC-i respons e was not diminished by the nitric oxide synthase inhibitor N-G-nitro- L-arginine methyl ester (10(-4) M). We conclude the exposure to ragwee d through the airways in rabbits with tgE to this allergen leads to an enhanced contractile response to EFS and a significant decrease in th e airways' NANC-i response when compared with normal or immune rabbit airways. In addition, a significant decrease in NANC-i response occurs in tracheal segments from rabbits after parenteral ragweed immunizati on alone. This decrease in NANC-i may be one mechanism contributing to the altered airway responsiveness associated with IgE immune states. (C) 1994 Wiley-Liss, Inc.